Intravascular injection of contrast solutions is the de facto standard method for diagnosis of vasoocclusive disease. These agents have osmolar, chemotoxic, and anaphylactic risks. Substitution of gas as contrast medium has significant potential to avoid these recognized limitations of conventional contrast media solutions with high safety. Automated intravascular injection of various gases enables the development of novel imaging approaches with multiple imaging modalities (CT, ultrasound, MRI, and others). In particular, sequential and concomitant accumulation of intravenously injected gases in the pulmonary microvasculature and in the alveoli during single breath-hold offers a potential self-enhancing mechanism for direct perfusion imaging. We propose to develop an instrument for safe intravenous gas injection of gases in simulations and in the pulmonary vasculature of animals. Our goal is to realize the potential of automated gas injection as an alternative to liquid intravascular contrast and achieve greater safety, better imaging performance, and possible reduction or elimination of radiation. The performance of a prototype gas injector will be tested for reliable and safe delivery of CO2, nonpolarized stable Xe, and hyperpolarized Xe in an ex-vivo flow circuit. In vivo imaging performance will be evaluated and optimized using temporal Volumetric Image Display and Analysis in pigs without and with pulmonary emboli. Electron beam cine-CT will be used with injections of CO2 and stable Xe, MRI will be used with injections of hyperpolarized Xe. On completion, this project will provide a well characterized automated gas injection device with known imaging performance on administration of various gases. This device should find application for assessment of pulmonary embolism with contrast angiography when noninvasive and potentially radiation free three- dimensional vascular imaging modalities are preferred. The methodology can be expanded to gas- enhanced imaging of the entire vasculature and endoluminal gas-enhanced therapeutic applications.